A logic-gated trispecific engager enhances macrophage killing of cancer cells in solid tumors - PubMed
7 hours ago
- #macrophage engager
- #solid tumors
- #cancer immunotherapy
- A trispecific macrophage engager (TrME) enhances macrophage killing of cancer cells in solid tumors.
- TrME activates the prophagocytic receptor LRP1 and blocks the antiphagocytic receptor SIRPα, creating an 'activate and block' AND logic gate.
- The TrME combines monovalent LRP1 activator calreticulin, anti-SIRPα scFv, and a tumor-associated antigen (TAA)-targeting arm via flexible linkers.
- Computational modeling identified an optimal conformation for robust cis-targeting and logic-gated signaling control.
- Delivery of mRNA encoding TAA-targeting TrME via lipid nanoparticles activates macrophages, inhibiting tumor growth and improving survival in mouse models.
- The study was funded by multiple grants from the National Natural Science Foundation of China and other provincial foundations.